No Long-Term Effects on Growth in Asthmatic Children Using Floventle

Question

You
start a 6 year old girl on Flovent and her parents read that this could
potentially affect her growth. Does Flovent have long-term effects
on growth in children with persistent asthma?

Clinical
Bottom Lines

Long-term administration (1 year) of inhaled fluticasone propionate
(100 micrograms and 200 micrograms/day) is well-tolerated in children
with persistent asthma.1

No statistically significant differences were noted between fluticasone
propionate and placebo treatment groups with respect to height measurement,
growth velocity, or skeletal age.

An overall difference of 0.42 cm/yr in mean change from baseline
in height between patients treated with fluticasone propionate 100 micrograms
and those treated with placebo could be attributable to a small drug
effect or withdrawal of poorly controlled, slower growing children from
the placebo group because of worsening asthma control.

It remains appropriate to use the minimum effective dose of inhaled
corticosteroid in children and to monitor growth of children by using
stadiometry during treatment, particularly at higher doses.

Summary of Key Evidence

In a double-blind, randomized, parallel-group, multicenter study,
325 prepubescent children with persistent asthma and normal growth rates
were treated with placebo or inhaled fluticasone propionate powder (50
or 100 micrograms) administered twice daily by a breath-actuated device
for 1 year.

Growth was evaluated monthly; other safety variables and pulmonary
function were evaluated periodically.

Children eligible for the study had normal growth rates as defined
by height measurements (one measurement taken 6 to 18 months before
the study and one at screening) between the 5th and 95th percentiles
and growth velocity between the 10th and 97th percentiles.

Changes in height at the end of treatment were comparable to normal
growth rates for patients of similar age.

Skeletal maturation at baseline was comparable to chronologic age
at baseline for all treatment groups. At the end of 1 year of
treatment, the mean change from baseline in skeletal age was 1.13 +/-
0.06 years, 1.13 +/1 0.06 years, and 0.95 +/- 0.05 years in patients
treated with twice daily doses of placebo, fluticasone propionate 50
micrograms, and fluticasone propionate 100 micrograms, respectively
(p=0.146, overall).

The target enrollment size of 90 patients per treatment group was
chosen to provide 80% power of detecting a 1.0 cm per year difference
in height velocity between treatment groups.

Only 66% of prepubescent patients in the placebo group completed
the 52-seek treatment period compared with more than 80% of patients
in each of the two treatment groups.

No significant difference were noted among treatment groups with
respect to drug-related adverse events, clinical laboratory tests, and
ophthalmologic examinations.

Additional
Comments

All patients remaining in the study were prepubescent as defined by
a sexual maturity rating of 1 in any Tanner classification.

Of the 268 prepubescent patients remaining in the study, similar clinical
characteristics at baseline existed across treatment groups.

Patients had a history of persistent asthma for at least 3 months--patients
were required to have an FEV1 of at least 60% of predicted.

Patients were excluded if they had received systemic, intranasal,
or ophthalmic corticosteroids within the month before study entry or
had cataracts, glaucoma, or any other significant concurrent disease
or condition. Previous systemic corticosteroid use was limited
to a total of 60 days within the 2 years before study entry.

Patients on a maintenance dose of inhaled corticosteroids were required
to maintain a fixed dosage regimen for at least 3 months before screening.
Patients not on a fixed regimen were not allowed to use inhaled corticosteroid
for more than 60 days within 2 years before screening.

The data presented in the current study are consistent with those
of other studies in which growth was not impaired in children who were
treated for at least 1 year with inhaled budesonide (Pulmicort) 200
or 400 micrograms/day or with beclomethasone dipropionate (Vanceril/Beclovent)
300 micrograms/day--"medium potency."

Growth was suppressed in children who received beclomethasone dipropionate
400 micrograms/day for 7 months, 400 micrograms/day for 1 year, or 200
micrograms/day to 800 micrograms/day for up to 6 years. However,
these three studies have been criticized for short duration, lack of
assessment of pubertal status, lack of an untreated control group, lack
of baseline growth velocity measurements, use of chronologic age
versus bone age assessments, and differences between treatment groups
in baseline heights and ages.

The design of this study represents the first of its kind to address
multiple confounding factors that weakened the results of previous growth
studies